COVID-19 has many symptoms, but one of the most characteristic of all is a new, often dry, continuous cough. That’s because it is (among other things) a respiratory illness, affecting every inch of our airways, from our sinuses to our lungs.
Now, we are able to see in stunning detail exactly how it affects our lungs. Using a revolutionary new technology, known as Hierarchical Phase-Contrast Tomography (HiP-CT), researchers have been able to scan a number of human organs – one of which was the lung of an organ donor who died from COVID-19. The result is an image more precise than a hospital CT scan, revealing the true damage caused by the virus at a cellular level.
“Shortly after the beginning of the global pandemic we demonstrated that Covid-19 is a systemic vascular disease using histopathological (optical imaging of tissue) and molecular methods,” explained Maximilian Ackermann, who uses the technique in a clinical setting. “However, these techniques did not adequately address the extent of the changes and clotting in fine blood vessels of whole lungs.”
To create the images, the researchers had to look outside of the traditional hospital setting – the HiP-CT technique instead relies on a real-life particle accelerator. The European Synchrotron Research Facility (ESRF) in Grenoble, France, stepped up to the challenge: after a recent (and wonderfully named) Extremely Brilliant Source upgrade (ESRF-EBS), the Synchrotron emits the brightest source of X-rays in the world – 100 billion times brighter than a hospital X-ray.
“The idea to develop this new HiP-CT technique came after the beginning of the global pandemic, by combining several techniques that were used at the ESRF to image large fossils,” Paul Tafforeau, lead scientist at ESRF, said. “[U]sing the increased sensitivity of the new Extremely Brilliant Source at the ESRF … allows us to see in 3D the incredibly small vessels within a complete human organ, enabling us to distinguish in 3D a blood vessel from the surrounding tissue, and even to observe some specific cells.”
“This is a real breakthrough, as human organs have low contrast and so are very difficult to image in detail with the current available techniques,” Tafforeau added. “ESRF-EBS has allowed us to go from deciphering the secrets of fossils to seeing the human body as never before.”
Along with the COVID-19-ravaged lung, the researchers scanned a brain, lung, heart, two kidneys and a spleen, all of which are set to be displayed online in a new resource called the Human Organ Atlas. Backed by the Chan Zuckerberg initiative, the Atlas will also feature biopsies of a control lung and a COVID-19 lung, and will be available for use by both medical professionals and the public.
“The Atlas spans a previously poorly explored scale in our understanding of human anatomy, which is the centimeter to micron scale in intact organs,” said project lead Peter Lee. So far, he explained, clinical techniques such as CT and MRI scans are capable of resolving down to just under a millimeter – if you need more detail than that, you need to either use an electron microscope or its traditional equivalent. Both can “resolve structures with sub-micron accuracy,” Lee explained, “but only on small biopsies of tissue from an organ.”
“HiP-CT bridges these scales in 3D, imaging whole organs to provide new insights into our biological makeup,” said Lee.
But the Organ Atlas isn’t the only benefit of the project: the researchers believe that this bridging of scales in imaging can open many insights into diseases like cancer and Alzheimer’s disease. Eventually, they hope to be able to use machine learning and artificial intelligence to combine the HiP-CT scans with clinical CT and MRI imaging, allowing for faster and more accurate diagnoses from these traditional scans.
“The ability to see organs across scales like this will really be revolutionary for medical imaging,” said mechanical engineer Claire Walsh. “As we start to link our HiP-CT images to clinical images through AI techniques, we will - for the first time - be able to highly accurately validate ambiguous findings in clinical images.”
“For understanding human anatomy this is also a very exciting technique,” she added. “[B]eing able to see tiny organ structures in 3D in their correct spatial context is key to understanding how our bodies are structured and how they therefore function.”